Denosumab risks in CKD
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Denosumab carries a marked risk of profound, refractory hypocalcemia in advanced chronic kidney disease, particularly stages 4 to 5D and comorbid CKD-mineral and bone disorder. In these patients, impaired calcitriol synthesis and secondary hyperparathyroidism render systemic calcium homeostasis acutely dependent on continuous skeletal resorption. Rapid RANK-ligand inhibition abruptly halts osteoclastic efflux, precipitating dangerous calcium nadirs typically occurring two to ten weeks post-injection. Severe cases carry documented risks of lethal arrhythmias, seizures, and exacerbation of adynamic bone disease. Clinical management mandates rigorous pre-treatment evaluation of baseline mineral metabolism, aggressive replete therapy with calcitriol and calcium salts, and frequent post-dose biochemical surveillance.